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Connective Tissue Proper Won Taek Lee, M.D., Ph.D. Connective Tissue Characteristics 1. abundant intercellular substance 2. diversity of cellular components Connective Tissue Classification Connective Tissue Proper Adipose Tissue Specialized Connective Tissue Bone and Cartilage Blood and Hemopoietic Tissue Connective Tissue Proper Cellular Components Fixed cells Wandering cells Intercellular Substance (Matrix) Fibers Ground substance Cellular Components 1. Fibroblast - Fibrocyte 2. Macrophage system 3. Mast cell 4. Plasma cell 5. Adipose cell 6. Mesenchymal cell 6. Others: leukocytes, smooth muscle cell, pericytes Fibroblast - Fibrocyte blastic activity - intercellular substance ---- protein synthesizing cells in active state limited activity in resting stage (fibrocyte) -blast, -cyte change osteoblast - osteocyte chondroblast - chondrocyte cementoblastt - cementocyte Fibroblast - Fibrocyte Fibroblast - Fibrocyte Fibroblast Fibrocyte Function: Fibers (collaen, elastic) and ground substance (proteoglycan) production. Macrophage System high phagocytic activity ---- secondary lysosome precursor cell ---- blood monocyte Mononuclear phagocytic system (MPS) CTP ---------- histiocyte liver ---------- Kupffer cell lung ---------- dust cell (alveolar macrophage) bone --------- osteoclast CNS --------- microglia Placenta ----- Hofbauer cell Macrophage Mast Cell Large cell, 20-30 mm in diameter with small nucleus, filled with abundant secretory granules prominent Golgi Secretory (metachromatic) granule 0.3-0.5 mm in diameter storage of chemical mediators of immediate type immune response metachromasia due to heparin and other glycosaminoglycans Mast Cell Mast Cell Mast Cell IgE degranulation Plasma Cell Antibody (Ab) producing cell Protein synthesizing cell cart wheel (clock face) appearance ------ chromatin pattern cytoplasmic basophilia ------ abundant rER perinuclear halo ----- Golgi complex Chronic inflammatory cell humoral immune response Precursor cell ----- B lymphocyte Plasma Cell Plasma Cell Adipose (Fat) Cell White (unilocular) adipose cell 20-100 mm in diameter single central lipid droplet peripheral nucleus signet ring cell Brown (multilocular) adipose cell 15-25 mm in diameter abundant mitochondria and lipid droplet heat generation White Adipose (Fat) Cell White Adipose (Fat) Cell Brown Adipose (Fat) Cell Brown Adipose Cell Function Norepinephrine Adenyl cyclase activation Lipase activation Fatty acids release Oxidation in mitochondria Heat generation Mesenchymal Cell small stellate cell 7-10 mm in diameter not easily distinguished from fibrocyte Pluripotential (totipotential) stem cell precursor of connective tissue cell of embryonic mesenchyme small population of cells of mesenchyme persist into postnatal life and differntiate to form other CT cells Mesenchymal Cell Connective Tissue Fiber 1. Collagen fiber ---- type I collagen 2. Reticular fiber ---- type III collagen 3. Elastic fiber ------- elastin, fibrillin Collagen Fiber • Acidophilic thick, birefringent • Very resistant to traction - extensibility ---- 5% - very high tensile strength • Most abundant proteins of the body - 30-35% of dry body weight - 20% of total body proteins • High in glycine, alanine, proline, hydroxyproline, hydroxylysine poor in sulfur, no tryptophan Collagen Fiber dermis Collagen Fiber • Collagen fiber bundle Collagen Fiber --------------------------- 5-15 mm Collagen Fibril ------------------------ 0.3-2 mm Collagen Microfibril -------------- 5-20 nm Collagen Protofibril ------------ 4.5 nm Tropocollagen Molecules - 1.5 nm • Periodicity of Collagen Fibrils - longitudinal arrangement of tropocollagen molecules 0.6 D (38.4 nm) gap --- lacunar region - stepwise arrangement overapping region --- ~10% of tropocollagen length Collagen Fibrils Collagen Synthesis Intracellular Process Nucleus -------- mRNA transcription Ribosome ----- transcription of preprocollagen rER cisterna -- hydroxylation and glycosylation, formation of procollagen triple helix Golgi ------------ secretion of procollagen Extracellular Process Propeptidase convert procollagen to tropocollagen Process of Collagen Synthesis Major Collagen Types Type Procollagen morphology I [1(I)]2 2(I)] fiber (collagen) II [1(II)]3 fiber III [1(III)]3 IV [1(IV)]2 2(IV)] V VII Tissue Distribution Disease bone, skin, tendon, ligament, dentin, cementum osteogenesis imperfecta cartilage chondrodysplasia skin, arteries, fiber (reticular) reticular tissues and organs, liver Ehlers-Danlos syndrome type IV sheet basement membrane Alport's syndrome [1(V)]2 2(V)] fiber fetal tissues, placenta, interstitial tissues [1(VII)]3 anchoring fibril junction of epidermis and dermis epidermolysis bullosa Collagen Types Type I collagen Type IV collagen Collagen defects Scurvy – deficiency of Vitamine C, cofactor for proline hydroxylase Ehlers-Danlos syndrome type VI – faulty lysyl hydroxylation, kyposcoliosis Ehlers-Danlos syndrome type IV – defects in type III collagen, vascular abnormalities Ehlers-Danlos syndrome type IV – defects in procollagen peptidase, articular abnormalities Osteogenesis imperfecta – type I collagen gene mutation Chondrodysplasia – type II collagen gene mutation Alport’s syndrome – type IV collagen (BM) anomaly Collagen excess: Fibrosis, Kelloid, Cirrhosis Scurvy Vitamine C (cofactor for proline hydroxylase) Deficiency Scurvy – Historical disease James Lind (1716-1794) Ehlers-Danlos syndrome Defects in collagen synthesis – High elasticity Osteogenesis Imperfecta Alport’s syndrome Reticular Fiber • Argyrophilic, PAS-positive, thin (0.5-2 m) fiber Structural maintenance in expansile organ. • Type III Collagen 6-12% hexoses (1% in collagen type I) Collagen microfibrils + Proteogycan interfibrillar bridge • Immature Fiber Abundant in embryonic tissues and wound healing • Reticular Tissue, Glands, Large Vessels, Intestinal Wall • Ehlers-Danlos Type IV (Faulty transcription/translation of Type III Collagen) Reticular Fiber Elastic Fiber • 0.1-10 mm thick fiber • High Elasticity (rubber-like consistency) • Special stain: resorcin fuchsin, aldehyde fuchsin, van Gieson (mordant hematoxylin), and orcein • Distribution: Elastic Connective Tissue ligamentum nucha, ligamentum flava vocal ligaments, stylohyoid ligement elastic membrane and lamellae of artery elastic cartilage Elastic Fiber Elastin, central (Pars Amorpha) glycine (half), proline (10%), hydroxyproline desmosine, isodesmosine Microfibrils, peripheral (Pars Filamentosa) 11-13 nm in diameter Fibrillin: no isodesmosine, desmosine, hydroxyproline half-cystine residue, 5% neutral sugar Elastic Fiber Evolution Oxytalan Fiber oxytalan fiber microfibril no elastin Elaunin Fiber elastin deposition microfibril Elastic Fiber elastin, central microfibril, peripheral elaunin fiber elastic fiber Elastic Fiber Elastic Fiber central elastin and peripheral microfibrils Elastic Fiber elasticity stretch and relaxation Defects in Fibrillin – Marfan syndrome tall statue arachnoidactily Defects in Fibrillin – Marfan syndrome Marfan syndrome Pharaoh Akhenaten Abraham Lincoln Ground Substance Proteoglycan glycosaminoglycan (GAG) made of repeating disaccharide hexose+hexosamine core potein test tube brush shape sometimes linked to hyaluronic acid Structural Glycoprotein fibronectin, laminin, chondronectin Glycosaminoglycans (GAG) GAG hexuronic acid hexosamine Distribution hyaluronic acid D-glucuronic acid D-glucosamine cartilage, umbilical cord, synovial fluid, vitreous humor chondroitin-4sulfate D-glucuronic acid D-galactosamine cartilage, bone, cornea, skin, notochord, aorta chondroitin-6sulfate D-glucuronic acid D-galactosamine cartilage, umbilical cord, skin, aorta (media) dermatan sulfate L-iduronic acid, D-glucuronic acid D-galactosamine skin, tendon, aorta (adventitia) heparan sulfate D-glucuronic acid, D-galactosamine D-iduronic acid keratan sulfate D-galactose (corneal) keratan sulfate D-galactose (skeletal) aorta, lung, liver, basal lamina D-galactosamine cornea D-glucosamine cartilage, nucleus pulposus, annulus fibrosus Proteoglycan and Glycosaminoglycans (GAG) Structural Glycoprotein Fibronectin Laminin Extracellular and intracellular integrity fibronectin integrin interaction Extracellular Matrix and Cellular Interaction Connective Tissue Proper Classification Loose connective tissue Dense connective tissue dense regular connective tissue dense irregular connective tissue Loose Connective Tissue Dense Irregular Connective Tissue Dense Regular Connective Tissue
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